Packed Column Supercritical Fluid Chromatography/Mass Spectrometry for High-Throughput Analysis

Ventura, Manuel; Farrell, William; Aurigemma, Christine; Greig, Michael J.

doi:10.1021/ac981372h

Cited by 54 publications

(44 citation statements)

References 34 publications

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“…The authors concluded that the union of SFC with TOF -MS provided the maximum density of chemical information per unit time. Ventura et al (1999a) demonstrated a threefold reduction in analysis time of SFC/APCI -MS compared with that of LC/APCI -MS for high -throughput multicomponent combinatorial library mixtures. In addition, separation of library components was found to be improved in SFC compared to LC, albeit with modestly reduced sensitivity of SFC/APCI -MS relative to LC/ One of the main problems encountered in the development of preparative SFC instrumentation, as required for high -throughput purifi cation of diverse compounds, is the technology available to collect fractions.…”

Section: Sfc Applications For High -Throughput Analysismentioning

confidence: 99%

Supercritical Fluid Chromatography

Dai

Zhang

Wang‐Iverson

et al. 2012

ADME‐Enabling Technologies in Drug Design and Development

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Section: Sfc Applications For High -Throughput Analysismentioning

confidence: 99%

Supercritical Fluid Chromatography

Dai

Zhang

Wang‐Iverson

et al. 2012

ADME‐Enabling Technologies in Drug Design and Development

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“…Also, a suitable mobile phase and HPLC column must be selected. As an alternative to HPLC, supercritical fluid chromatography-mass spectrometry (SFC-MS) has been used for the high-throughput analysis of combinatorial libraries [18,19]. The advantages of SFC-MS relative to conventional LC-MS for the purification of combinatorial libraries of compounds are the lower viscosities and higher diffusivities of condensed CO 2 compared to HPLC mobile phases, and the ease of solvent removal and disposal after analysis.…”

Section: Lc-ms Purification Of Combinatorial Librariesmentioning

confidence: 99%

Mass Spectrometry and Drug Discovery

Breemen

Newsome

Dahl

2010

Burger's Medicinal Chemistry and Drug Discovery

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In the twenty‐first century, medicinal chemists are producing large numbers of organic compounds through a process called combinatorial chemistry and then testing them against pharmacological targets such as enzymes or receptors using high‐throughput screening. As a result, lead compounds can emerge from drug discovery programs in a few weeks instead of several years. Although a variety of spectroscopic and chromatographic techniques are used to support drug discovery, only HPLC or UHPLC combined with mass spectrometry (LC‐MS) are compatible with virtually all drug‐like molecules. In addition to providing a universal means to characterize drug molecules based on molecular mass and structural features, mass spectrometry provides high throughput. With the development of routine LC‐MS interfaces and ionization techniques such as electrospray and atmospheric pressure chemical ionization, mass spectrometry has also become an ideal HPLC detector for the analysis of combinatorial libraries. Furthermore, a variety of mass spectrometry‐based screening assays have been developed to screen complex mixtures of compounds including natural product extracts as a means of expanding the molecular diversity of drug leads. The use of mass spectrometry in support of combinatorial library synthesis and purification is addressed as well as screening applications such as frontal affinity chromatography‐mass spectrometry, gel permeation chromatography‐LC‐MS, affinity chromatography‐mass spectrometry, and pulsed ultrafiltration mass spectrometry. Since drug development issues such as metabolic stability and the formation of reactive metabolites are now being considered during the drug discovery process, some applications of mass spectrometry to early drug development are addressed.

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“…Otherwise, molecular ion species might not be formed. Alternatively, supercritical fluid chromatography-mass spectrometry (SFC-MS) has been used for the high-throughput analysis of combinatorial libraries [11,12], and it offers benefits for use during mass spectrometry-based purification of combinatorial libraries. The advantages of SFC-MS relative to conventional LC-MS are (1) lower viscosities and higher diffusivities of condensed CO 2 than HPLC mobile phases, and (2) ease of solvent removal and disposal after analysis.…”

Section: Mass Spectrometry-based Hplc Purification Of Combinatorial Lmentioning

confidence: 99%

Analysis and screening of combinatorial libraries using mass spectrometry

Shin

Breemen

2001

Biopharm & Drug Disp

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Mass spectrometry is a highly selective and high throughput analytical technique that is ideally suited for the identification and purity determination of large numbers of compounds prepared using combinatorial chemistry or for the dereplication of natural products. Compounds may be characterized based on molecular weight, elemental composition and structural features based on fragmentation patterns. When coupled to a separation technique such as highperformance liquid chromatography (HPLC) or capillary electrophoresis, mass spectrometric applications may be expanded to include analysis of complex mixtures. However, the slower speed of the separation step reduces the throughput of the analysis. This review concerns the application of mass spectrometry to the characterization of combinatorial libraries and the screening of library and natural product mixtures. Strategies to enhance the throughput of LC-MS are discussed including fast HPLC and parallel LC-MS. Also, mass spectrometry-based screening methods are described including frontal affinity chromatography-mass spectrometry, gel permeation chromatography LC-MS, direct electrospray mass spectrometry of receptor-ligand complexes, affinity chromatography-mass spectrometry, and pulsed ultrafiltration mass spectrometry.

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Packed Column Supercritical Fluid Chromatography/Mass Spectrometry for High-Throughput Analysis

Cited by 54 publications

References 34 publications

Supercritical Fluid Chromatography

Supercritical Fluid Chromatography

Mass Spectrometry and Drug Discovery

Analysis and screening of combinatorial libraries using mass spectrometry

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